Redundant role of TLR9 for anti-Candida host defense.
The role of Toll-like receptor-9 (TLR9) in the recognition of Candida albicans and anti-Candida host defense was investigated in a murine model of disseminated candidiasis and in human peripheral blood mononuclear cells (PBMC). Blocking TLR9 by a specific inhibitor of human TLR9 or stimulation of cells isolated from TLR9-deficient (TLR9-/-) mice resulted in a 20-30% reduction in cytokine production induced by C. albicans. However, this defect was not accompanied by differences in mortality and organ fungal growth between TLR9-/- and TLR9+/+ mice. In conclusion, TLR9 is a pathogen-recognition receptor for C. albicans, and TLR9 is involved in the induction of cytokines in response to C. albicans. However, the cytokine defect in TLR9-/- mice is compensated by alternative pathways, and the TLR9-dependent pathway seems to be redundant in the disseminated candidiasis model in mice.
van de Veerdonk
Frank Leo
FL
F.veerdonk@aig.umcn.nl
Netea
Mihai G
MG
Jansen
Trees J
TJ
Jacobs
Liesbeth
L
Verschueren
Ineke
I
van der Meer
Jos W M
JW
Kullberg
Bart Jan
BJ
D000818:Animals; D002176:Candida albicans; D002177:Candidiasis / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D006801:Humans; D007113:Immunity, Innate; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000235:genetics; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016376:Oligonucleotides, Antisense / Q000235:genetics; D010587:Phagocytosis / Q000235:genetics / Q000276:immunology; D051217:Toll-Like Receptor 9 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*
D016207:Cytokines; D016376:Oligonucleotides, Antisense; D051217:Toll-Like Receptor 9